1. Field of the Invention
The present invention relates generally to fluidic processing and, more particularly, to methods and apparatuses to controllably inject fluid packets onto a surface. Even more particularly, the present invention relates to methods and apparatuses for programmably injecting fluid packets onto a surface using dielectrophoretic forces.
2. Description of Related Art
Chemical protocols often involve a number of processing steps including metering, mixing, transporting, division, and other manipulation of fluids. For example, fluids are often prepared in test tubes, metered out using pipettes, transported into different test tubes, and mixed with other fluids to promote one or more reactions. During such procedures, reagents, intermediates, and/or final reaction products may be monitored, measured, or sensed in analytical apparatus. Microfluidic processing generally involves such processing and monitoring using minute quantities of fluid. Microfluidic processing finds applications in vast fields of study and industry including, for instance, diagnostic medicine, environmental testing, agriculture, chemical and biological warfare detection, space medicine, molecular biology, chemistry, biochemistry, food science, clinical studies, and pharmaceutical pursuits.
Current approaches directed at fluidic processing exhibit several shortcomings. One current approach to microfluidic processing utilizes a number of microfluidic channels that are configured with microvalves, pumps, connectors, mixers, and detectors. While devices using micro-scale implementations of these traditional approaches may exhibit at least a degree of utility, vast room for improvement remains. For instance, current microfluidic devices lack flexibility for they rely upon a fixed pathway of microchannels. With fixed pathways, devices are limited in the number and type of tasks they may perform. Also, using fixed pathways makes many types of metering, transport, and manipulation difficult. With traditional devices, it is difficult to partition one type of sample from another within a channel.
Other current approaches involve electrical properties of materials. In particular, certain electrical properties of materials have been employed to perform a limited number of fluidic processing tasks. For example, dielectrophoresis has been utilized to aid in the characterization and separation of particles, including biological cells. An example of such a device is described in U.S. Pat. No. 5,344,535 to Betts, incorporated herein by reference. Betts establishes dielectrophoretic collection rates and collection rate spectra for dielectrically polarizable particles in a suspension. Particle concentrations at a certain location downstream of an electrode structure are measured using a light source and a light detector, which measures the increased or decreased absorption or scattering of the light which, in turn, indicates an increase or decrease in the concentration of particles suspended in the fluid. Although useful for determining particle dielectrophoretic properties, such a system is limited in application. In particular, such a system does not allow for general fluidic processing involving various interactions, sometimes performed simultaneously, such as metering, mixing, fusing, transporting, division, and general manipulation of multiple reagents and reaction products.
Another example of using certain electrical properties for specific types of processing is disclosed in U.S. Pat. No. 5,632,957 to Heller et al., incorporated herein by reference. There, controlled hybridization may be achieved using a matrix or array of electronically addressable microlocations in conjunction with a permeation layer, an attachment region and a reservoir. An activated microlocation attracts charged binding entities towards an electrode. When the binding entity contacts the attachment layer, which is situated upon the permeation layer, the functionalized specific binding entity becomes covalently attached to the attachment layer. Although useful for specific tasks such as DNA hybridization, room for improvement remains. In particular, such a system, utilizing attachment sites for certain binding entities is designed for particular applications and not for general fluidic processing of a variety of fluids. More specifically, such a system is designed for use with charged binding entities that interact with attachment sites.
Another example of processing is disclosed in U.S. Pat. No. 5,126,022 to Soane et al., incorporated herein by reference. There, charged molecules may be moved through a medium that fills a trench in response to electric fields generated by electrodes. Although useful for tasks such as separation, room for improvement remains in that such devices are not well suited for performing a wide variety of fluidic processing interactions on a wide variety of different materials.
There are other examples of using dielectrophoresis for performing specific, limited fluidic processing tasks. U.S. Pat. No. 5,795,457 to Pethig and Burt, incorporated herein by reference, disclose a method for promoting reactions between particles suspended in liquid by applying two or more electrical fields of different frequencies to electrode arrays. While perhaps useful for facilitating certain interactions between many particles of different types, the method is not well suited for general fluidic processing. U.S. Pat. No. 4,390,403 to Batchelder, incorporated herein by reference, discloses a method and apparatus for manipulation of chemical species by dielectrophoretic forces. Although useful for inducing certain chemical reactions, its flexibility is limited, and it does not allow for general, programmable fluidic processing.
Methods and apparatuses to address many, if not all, of the shortcomings addressed above are disclosed in pending U.S. patent application Ser. No. 09/249,955, filed Feb. 12, 1999, now U.S. Pat. No. 6,294,063 and entitled, “Method And Apparatus for Programmable Fluidic Processing,” which is incorporated herein by reference in its entirety. There, techniques are disclosed that relate to the manipulation of a packet of material using a reaction surface, an inlet port, means for generating a programmable manipulation force, a position sensor, and a controller. In one embodiment of that disclosure, the material is introduced onto the reaction surface with the inlet port. The material is compartmentalized to form a packet. The position of the packet is sensed with the position sensor. A programmable manipulation force (which, in one embodiment, may involve a dielectrophoretic force) is applied to the packet at a certain position with the means for generating a programmable manipulation force, which is adjustable according to the position of the packet by the controller. The packet may then be programmably moved according to the programmable manipulation force along arbitrarily chosen paths.
U.S. Pat. No. 5,858,192, entitled “Method and apparatus for manipulation using spiral electrodes”, filed Oct. 18, 1996 and issued Jan. 12, 1999; U.S. Pat. No. 5,888,370 entitled “Method and apparatus for fractionation using generalized dielectrophoresis and field flow fractionation”, filed Feb. 23, 1996 and issued Mar. 30, 1999; U.S. Pat. No. 5,993,630 entitled “Method and apparatus for fractionation using conventional dielectrophoresis and field flow fractionation,” filed Jan. 31, 1996 and issued Nov. 30, 1999; U.S. Pat. No. 5,993,632 entitled “Method and apparatus for fractionation using generalized dielectrophoresis and field flow fractionation,” filed Feb. 1, 1999 and issued Nov. 30, 1999; and U.S. patent application Ser. No. 09/395,890 entitled “Method and apparatus for fractionation using generalized dielectrophoresis and field flow fractionation,” filed Sep. 14, 1999 now U.S. Pat. No. 6,287,832 are each herein incorporated by reference.
U.S. “Patent Application” with co-pending patent application Ser. No. 09/882,805 entitled “Method and apparatus for combined magnetophoretic and dielectrophoretic manipulation of analyte mixtures,” filed Jun. 14, 2001; U.S. “Patent Application” with co-pending patent application Ser. No. 09/883,112 entitled “Dielectrically-engineered microparticles,” filed Jun. 14, 2001; and U.S. Pat. No. 6,790,330 entitled “Systems and methods for cell subpopulation analysis,” filed Jun. 14, 2001 are each herein incorporated by reference.
The techniques disclosed in U.S. patent application Ser. No. 09/249,955 now U.S. Pat. No. 6,294,063 offer significant advantages over the traditional methods discussed above. For instance, they permit the fluidic processing of minute quantities of samples and reagents. The disclosed apparatus need not use conventional hardware components such as valves, mixers, pump. The disclosed apparatus may be readily miniaturized and its processes may be automated or programmed. The disclosed apparatus may be used for many different types of microfluidic processing and protocols, and it may be operated in parallel mode whereby multiple fluidic processing tasks and reactions are performed simultaneously within a single chamber. Because it need not rely on narrow tubes or channels, blockages may be minimized or eliminated. Further, if obstructions do exist, those obstructions may be located and avoided with position sensing techniques.
In order to use the apparatus disclosed in U.S. patent application Ser. No. 09/249,955, now U.S. Pat. No. 6,294,063 a material must be introduced onto the reaction surface. As is disclosed in U.S. patent application Ser. No. 09/249,955, now U.S. Pat. No. 6,294,063 this may be done using an inlet port. The inlet port may simply be an opening in a wall, or, alternatively, it may be a syringe needle, a micropipette, a tube, an inkjet injector, or the like.
Although using a syringe, a micropipette, or the like allows for injection of material onto the surface, shortcomings remain. For instance, such an inlet does not always provide for systematic, controllable injection of material. In particular, using existing devices and techniques (including those disclosed in U.S. patent application Ser. No. 09/249,955 now U.S. Pat. No. 6,294,063) does not always ensure that a controllable, single drop is injected at a time. Rather, existing technology often results in the injection of one drop at one time, two drops together at another time, etc. Hence, the controllability and metering capabilities of existing technology is not completely adequate. Without controllable packet injection, the accuracy and repeatability of certain microfluidic processing tasks may suffer.
In light of the above, it would be advantageous to provide for technology in which metered packets of material could be systematically injected onto a surface in a reliable, repeatable manner. It would further be advantageous is the method of injection were automated so that processing could take place with little, or no operator intervention. Such advantages would benefit not only the microfluidic processing contemplated in U.S. patent application Ser. No. 09/249,955, now U.S. Pat. No. 6,294,063 but also in all realms of fluidic processing. In particular, such advantages would benefit any field in which a controllable manner of injecting packets of materials is desired.
Any problems or shortcomings enumerated in the foregoing are not intended to be exhaustive but rather are among many that tend to impair the effectiveness of previously known processing and fluid injection techniques. Other noteworthy problems may also exist; however, those presented above should be sufficient to demonstrated that apparatus and methods appearing in the art have not been altogether satisfactory and that a need exists for the techniques disclosed herein.